Abstract
Age-related decline in stem cell function is observed in many tissues from invertebrates to humans. While cell intrinsic alterations impair stem cells, aging of the stem cell niche also significantly contributes to the loss of tissue homeostasis associated with reduced regenerative capacity. Hub cells, which constitute the stem cell niche in the Drosophila testis, exhibit age-associated decline in number and activities, yet underlying mechanisms are not fully understood. Here we show that Lin28, a highly conserved RNA binding protein, is expressed in hub cells and its expression dramatically declines in old testis. lin28 mutant testes exhibit hub cell loss and defective hub architecture, recapitulating the normal aging process. Importantly, maintained expression of Lin28 prolongs hub integrity and function in aged testes, suggesting that Lin28 decline is a driver of hub cell aging. Mechanistically, the level of unpaired (upd), a stem cell self-renewal factor, is reduced in lin28 mutant testis and Lin28 protein directly binds and stabilizes upd transcripts, in a let-7 independent manner. Altogether, our results suggest that Lin28 acts to protect upd transcripts in hub cells, and reduction of Lin28 in old testis leads to decreased upd levels, hub cell aging and loss of the stem cell niche.
Highlights
Stem cells, which are characterized by their ability to self-renew, present in most adult tissues produce daughter stem cells and differentiated cells
At the anterior tip of the Drosophila testis, hub cells assemble to constitute the niche that supports two stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs), with each GSC surrounded by two CySCs (Fig. 1A) [31, 32]
We found that Lin28 is expressed in the hub cells of the stem cell niche in the 3rd instar larva and young adult testis, while it is not expressed in other somatic and germline cells in this organ (Fig 1C, D; Fig. S1C)
Summary
Stem cells, which are characterized by their ability to self-renew, present in most adult tissues produce daughter stem cells and differentiated cells. With these unique properties, stem cells replenish aged cells to maintain tissue homeostasis throughout lifespan. Majority of stem cells reside in a specific microenvironment, the stem cell niche, which provides factors responsible for maintenance and differentiation of stem cells in a controlled and coordinated manner. These include local signals that ensure stem cell selfrenewal and adhesion of stem cells to their niche compartment.
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